AB1481 EMERALD STUDY DESIGN: A TWO-COHORT, OPEN-LABEL, SINGLE-ARM STUDY OF EMAPALUMAB, AN ANTI–INTERFERON-Γ (IFNΓ) MONOCLONAL ANTIBODY, IN PATIENTS WITH MACROPHAGE ACTIVATION SYNDROME (MAS) IN RHEUMATIC DISEASES
Authors: F. De Benedetti, R. Krmar, R. Kanceva, A. Grom
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> MAS is a severe, life-threatening form of secondary hemophagocytic lymphohistiocytosis associated with rheumatic diseases such as Still's disease (systemic juvenile idiopathic arthritis or adult-onset Still's disease) and systemic lupus erythematosus (SLE). IFNγ has been implicated in the underlying pathology of both conditions. High-dose glucocorticoids (GCs) are the standard first-line treatment for MAS; however, there is no standardized approach to treating patients who are refractory to high-dose GCs. In a pilot study of 9 patients with an inadequate response to high-dose GCs, IFNγ was rapidly neutralized, and MAS controlled, following emapalumab administration (NCT03311854). Emapalumab also had a favorable safety profile. <h3>Objectives</h3> To present the design of a study enrolling patients with MAS in Still's disease and SLE with the aim of evaluating the efficacy and safety of emapalumab. <h3>Methods</h3> EMERALD (NCT05001737) is an open-label, single-arm, multicenter, phase 2/3 interventional study enrolling pediatric and adult patients with MAS and an inadequate response to high-dose GCs into two cohorts: MAS in Still's disease (n=25) and MAS in SLE (n=16). Key eligibility criteria vary by cohort and phase (Table 1). Each cohort is a single-arm study comprising two phases: an optional run-in phase and an interventional phase. Patients are treated with high-dose GCs during the run-in phase and followed until MAS remission, inadequate response, or 12 weeks (whichever occurs first). Eligible patients enrolled in the interventional phase are treated with emapalumab intravenously for 4 weeks (6 mg/kg on Day 1; 3 mg/kg every 3 days from Days 4–16, then 3 mg/kg twice weekly from Days 17–28) or until protocol-defined complete response (CR). Patients will be followed up for 1 year after study completion. <h3>Results</h3> Protocol-defined CR at Week 8 after first emapalumab administration is the primary endpoint of the EMERALD study. Secondary efficacy endpoints include GC tapering, survival, time to first CR, overall response (CR and partial response), time to first overall response, MAS recurrence, pharmacokinetic/pharmacodynamic profile of emapalumab, and patient-reported outcomes. Adverse events, abnormal laboratory parameters, and anti-drug antibodies will be monitored as safety endpoints. <h3>Conclusion</h3> The ongoing EMERALD study is designed to address the unmet need for efficacious and safe therapies for the treatment of MAS, particularly for patients who are refractory to high-dose GCs. <h3>Acknowledgements</h3> Medical writing assistance was provided by Blair Hesp PhD CMPP of Kainic Medical Communications Ltd. (Dunedin, New Zealand), which was funded by Sobi AG (Basel, Switzerland). <h3>Disclosure of Interests</h3> Fabrizio De Benedetti Consultant of: Consultant for AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis, Novimmune, Grant/research support from: Research grants from AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis, Novimmune, Rafael Krmar Employee of: Employee of Swedish Orphan Biovitrum AB, Radmila Kanceva Employee of: Employee of Swedish Orphan Biovitrum AG, Alexei Grom Consultant of: Consultant for Novartis, AB2 Bio, Novimmune, Sobi.